Dementia risk factors for Australian baby boomers

Baby boomers are individuals born in the years 1946 to 1965. The objective of this paper was to define the risk factors for dementia and Alzheimer’s disease (AD) and their relevance to Australian baby boomers, with the aim of providing evidence-based guidelines for dementia prevention. A series of PubMed searches (1994–2010) were conducted with relevant key words. Data was included from the Australian Bureau of Statistics (ABS) in relation to baby boomers in Australia. Article titles and abstracts were assessed by two reviewers for inclusion. Searches through ABS revealed no specific study on baby boomers at a national level; information was only available for Western Australia, South Australia and Queensland. A number of genetic and non-genetic risk factors for dementia were identified most of which remain controversial and require further study. We did not identify significant differences in the prevalence and incidence of dementia in those under 65 years in Queensland, South Australia and Western Australia. There were no correlations of risk factors and dementia between the Australian states. Modification of risk factors has not been proven to reduce the incidence and prevalence of dementia and AD in baby boomers. Nevertheless, on available evidence, we recommend: i) active management of cardiovascular risk factors such as hypertension; ii) the encouragement of a healthy lifestyle (eg, weight reduction, exercise) as offering the best pathways to reduce the emerging dementia risk for baby boomers. The implications are that activities promoting a healthy heart might lead to a healthy brain and help to prevent dementia

The clinical utility of gene testing for Alzheimer's disease

Alzheimer's disease (AD) is the largest cause of dementia, affecting 35.6 million people in 2010. Amyloid precursor protein, presenilin 1 and presenilin 2 mutations are known to cause familial early-onset AD, whereas apolipoprotein E (APOE) ε4 is a susceptibility gene for late-onset AD. The genes for phosphatidylinositol-binding clathrin assembly protein, clusterin and complement receptor 1 have recently been described by genome-wide association studies as potential risk factors for late-onset AD. Also, a genome association study using single neucleotide polymorphisms has identified an association of neuronal sortilin related receptor and late-onset AD. Gene testing, and also predictive gene testing, may be of benefit in suspected familial early-onset AD however it adds little to the diagnosis of late-onset AD and does not alter the treatment. We do not recommend APOE ε4 genotyping

The impact of COVID-19 on community neurology patients

BackgroundThe COVID-19 pandemic has had a worldwide impact. People with neurological disorders are at an increased risk of severe infection and consequent mortality. In this study we investigated the impact of COVID-19 on community neurology patients in the absence of direct infection with the virus to see if their wellbeing was affected.AimsTo determine whether and how the COVID-19 pandemic affected people with neurological disorders, in the absence of COVID-19 infection.Methods A prospective survey of patients with neurological conditions to evaluate the impact of the COVID-19 pandemic on their quality of life, physical and mental wellbeing, access to goods/services and areas of unmet needs relating to the pandemic. The survey was completed by 243 community neurology patients in Perth, Western Australia from April to June 2020.Results Most respondents reported that COVID-19 impacted their daily life (80.7 per cent) and family relationships (73.1 per cent). 10.3 per cent of patients had a substantial effect on their access to facilities such as the gym, and services such as physiotherapy; as well as access to finances (7 per cent) and care (5.8 per cent); whilst anxiety was increased to a minor degree in over half of patients (55.97 per cent). Unclear public health information and guidelines, social isolation and disruption to routine were also identified as difficulties.ConclusionDespite the absence of direct infection with COVID-19, many neurology patients experienced physical and emotional detriment as a result of the pandemic. This study identified the need for organisation and amendment to provisions of neurological services in preparation for future pandemics

C9ORF72 repeat expansion in Australian and Spanish frontotemporal dementia patients

A hexanucleotide repeat expansion in C9ORF72 has been established as a common cause of frontotemporal dementia (FTD). However, the minimum repeat number necessary for disease pathogenesis is not known. The aims of our study were to determine the frequency of the C9ORF72 repeat expansion in two FTD patient collections (one Australian and one Spanish, combined n = 190), to examine C9ORF72 expansion allele length in a subset of FTD patients, and to examine C9ORF72 allele length in ‘non-expansion’ patients (those with <30 repeats). The C9ORF72 repeat expansion was detected in 5–17% of patients (21–41% of familial FTD patients). For one family, the expansion was present in the proband but absent in the mother, who was diagnosed with dementia at age 68. No association was found between C9ORF72 non-expanded allele length and age of onset and in the Spanish sample mean allele length was shorter in cases than in controls. Southern blotting analysis revealed that one of the nine ‘expansion-positive’ patients examined, who had neuropathologically confirmed frontotemporal lobar degeneration with TDP-43 pathology, harboured an ‘intermediate’ allele with a mean size of only ~65 repeats. Our study indicates that the C9ORF72 repeat expansion accounts for a significant proportion of Australian and Spanish FTD cases. However, C9ORF72 allele length does not influence the age at onset of ‘non-expansion’ FTD patients in the series examined. Expansion of the C9ORF72 allele to as little as ~65 repeats may be sufficient to cause disease.Carol Dobson-Stone, Marianne Hallupp, Clement T. Loy, Elizabeth M. Thompson, Eric Haan, Carolyn M. Sue, Peter K. Panegyres, Cristina Razquin, Manuel Seijo-Martínez, Ramon Rene, Jordi Gascon, Jaume Campdelacreu, Birgit Schmoll, Alexander E. Volk, William S. Brooks, Peter R. Schofield, Pau Pastor, John B. J. Kwo

Stochasticity, Entropy and Neurodegeneration

We previously suggested that stochastic processes are fundamental in the development of sporadic adult onset neurodegenerative disorders. In this study, we develop a theoretical framework to explain stochastic processes at the protein, DNA and RNA levels. We propose that probability determines random sequencing changes, some of which favor neurodegeneration in particular anatomical spaces, and that more than one protein may be affected simultaneously. The stochastic protein changes happen in three-dimensional space and can be considered to be vectors in a space-time continuum, their trajectories and kinetics modified by physiological variables in the manifold of intra- and extra-cellular space. The molecular velocity of these degenerative proteins must obey the second law of thermodynamics, in which entropy is the driver of the inexorable progression of neurodegeneration in the context of the N-body problem of interacting proteins, time-space manifold of protein-protein interactions in phase space, and compounded by the intrinsic disorder of protein-protein networks. This model helps to elucidate the existence of multiple misfolded proteinopathies in adult sporadic neurodegenerative disorders

A patient with Creutzfeldt-Jakob disease presenting with amyotrophy: a case report

INTRODUCTION: Creutzfeldt-Jakob disease (CJD) is an ultimately fatal, neurodegenerative disease caused by misfolded prion protein aggregation and accumulation. The development of amyotrophic features has been described in CJD, though rarely as an early or prominent feature. Consequently, the significance of amyotrophy in prion disease etiology remains unclear. CASE PRESENTATION: Our patient, a healthy 70-year-old French/Algerian man, presented to our hospital following a work-related fall and was admitted with lower limb skeletal muscle atrophy and fasciculations; the fasciculations progressed to involve the trunk, upper limbs and face. Within days, he developed evidence of a progressive ascending neurological syndrome and subsequent brain involvement with supranuclear palsy of upgaze, catalepsy and death 36 days after symptom onset. Amyotrophy remained the principle feature of his disease. Dementia started to develop within 10 days of the onset of his amyotrophy. Prion disease was confirmed at postmortem. CONCLUSIONS: Our observations suggest an unusual form of prion disease with prominent early involvement of anterior horn cells, ascending prion propagation in the central nervous system and a grave prognosis

Cerebrovascular risk factors in early-onset dementia

Alzheimer\u27s disease (AD) is the leading cause of dementia. Research into environmental factors is currently focused on cerebrovascular risk factors.1 Treatment of vascular risk factors has been associated with slower cognitive decline and reduced risk of AD in older populations.2 Genetics are important in rare genetically determined autosomal dominant familial patients with AD or frontotemporal dementia (FTD).3 Apolipoprotein E (APOE) is a risk factor for familial late-onset sporadic AD, but its role as a risk factor in younger populations is unclear. The role of APOE as a risk factor for FTD is controversial. Early-onset dementia is dementia that develops in individuals prior to the age of 65 years, and some studies suggest it is associated with a higher mortality. AD and FTD are the most common causes of dementia in this population.4 The onset of FTD may be characterised by behavioural change and speech disturbance, whereas AD is usually characterised by defective episodic memory. It is hypothesised that cerebrovascular risk factors, such as hypertension and diabetes, are associated with the development of early-onset Alzheimer\u27s disease (EOAD) but not early-onset FTD. We set out to investigate this hypothesis in a cohort of early-onset AD and FTD patients. The participants in this study are a cohort of 123 consecutive prospectively analysed early-onset dementia patients with clinically confirmed AD or FTD who gave informed consent. They are a subset of patients in a larger longitudinal study. Sixty-two patients had AD, and 61 had FTD. Patients were diagnosed using published criteria augmented by modern research criteria utilising MRI and functional imaging (brain SPECT, PET) combined with genetic analysis. Appropriate ethics approval was obtained

Early Dementia Screening

As the population of the world increases, there will be larger numbers of people with dementia and an emerging need for prompt diagnosis and treatment. Early dementia screening is the process by which a patient who might be in the prodromal phases of a dementing illness is determined as having, or not having, the hallmarks of a neurodegenerative condition. The concepts of mild cognitive impairment, or mild neurocognitive disorder, are useful in analyzing the patient in the prodromal phase of a dementing disease; however, the transformation to dementia may be as low as 10% per annum. The search for early dementia requires a comprehensive clinical evaluation, cognitive assessment, determination of functional status, corroborative history and imaging (including MRI, FDG-PET and maybe amyloid PET), cerebrospinal fluid (CSF) examination assaying Aβ1–42, T-τ and P-τ might also be helpful. Primary care physicians are fundamental in the screening process and are vital in initiating specialist investigation and treatment. Early dementia screening is especially important in an age where there is a search for disease modifying therapies, where there is mounting evidence that treatment, if given early, might influence the natural history—hence the need for cost-effective screening measures for early dementia